Various dosage forms have meet proposed for drugs which require long-term repeated administration. For example, JP-A 57-118512 (U.S. Pat. No. 4,675,189) discloses microencapsulation of a drug by phase separation process using a coacervation agent such as mineral oils, vegetable oils or the like. However, the microcapsules obtained by this technique have a disadvantage that they tend to readily adhere to each other with low-shear in the course of production. Further, the large scale production thereof is difficult because a lot of solvent is used.
The traditional microencapsulation method which comprises formation of a three-phase emulsion containing a drug, followed by microencapsulation thereof by an in-water drying process to obtain microcapsules is mentioned in JP-A 60-100516 (U.S. Pat. No. 4,652,441). Although this technique improves the above disadvantage of adhesion, some points to be improved still remain. Namely, it is difficult to obtain microcapsules having a high drug content because, in the case of a water-soluble drug, the drug leaks out to the outer aqueous phase and the entrapping ratio thereof drops. In the case of both water-soluble and fat-soluble drugs, the in water drying process takes a long period of time, and a freeze-drying step is essential for pulverization. Further, in general, the microcapsules thus obtained have a large initial release rate of a drug. Furthermore, the microcapsules tend no be readily influenced by scaling up of the production and large scale treatment is difficult.
On the other hand, there are reports relating to microencapsulation by spray drying with one nozzle. However, in these reports, the initial release rate of a drug is large. In addition the desired prolonged release over a long period of time is not achieved and there is a problem that the large amount of microcapsules often aggregate to each other and adhere to a spray dryer.